What is autoimmune disease?
An autoimmune disease is a disease which involves a failure/breakdown in the part of the immune system which maintains tolerance to self-tissues.
Who can develop autoimmune disease?
What characterises autoimmune disease in terms of mortality and morbidity?
Low mortality but very high morbidity.
Is there a cure for autoimmune disease?
No- therapies are managed on a symptomatic basis rather than a cure basis.
What is the loss of tolerance in autoimmune disease usually caused by?
Abnormal selection or lack of control of self-reactive lymphocytes.
What are hypersensitivity responses?
Hypersensitivity responses are hyper (too much) responses from the immune system- they may produce tissue injury and cause serious disease.
What are the 4 categories of hypersensitivity response?
I, II , III , IV
What types of hypersensitivity response are antibody-mediated?
I , II , III
What types of hypersensitivity response are T-cell mediated?
What types of hypersensitivity responses do autoimmune diseases usually tend to fall into?
II , III , IV
What do Type I hypersensitivity reactions involve?
What happens during Type I hypersensitivity reactions?
Initiated by allergen, stimulating TH2 reactions and IgE production. IgE binds to a FceR1 protein and sensitises mast cells to produce an immune response.
What do Type I reactions stimulate?
TH2 reactions and IgE binding to FceR1 proteins to sensitise mast cells.
What protein does IgE bind to in order to sensitise mast cells?
What are the effects of mast cell stimulation?
Vasodilation, bronchioconstriction, oedema, vascular congestion.
What is seen in the immediate hypersensitivity reaction to allergy?
IgE mediation of mast cells to produce vasodilation/oedema/vascular congestion.
What is seen in the late-phase hypersensitivity reaction to allergy?
Inflammatory infiltrate rich in eosinophils, neutrophils, and T-cells.
When does an immediate hypersensitivity reaction occur?
Within minutes of allergen exposure.
When does a late-phase hypersensitivity reaction occur?
Within 2-24 hours of allergen exposure.
What is atopy?
Predisposition to allergy- patients more susceptible to autoimmune conditions such as asthma/eczema/thyroiditis.
What is higher in atopic patients?
What do Type II hypersensitivity reactions involve?
What happens in Type II hypersensitivity reactions?
Mediated by IgG/IgM antibodies binding to cell-surface antigens or matrix-associated antigens on basement membrane. This results in complement leading to the inflammatory response or involvement with cytotoxic T-cells.
What are Type II hypersensitivity reactions mediated by?
IgG/IgM antibodies binding to cell/matrix antigens.
What does mediation result in within Type II hypersensitivity reactions?
Complement- inflammatory response
Cytotoxic cell involvement.
Can Type II reactions include autoimmune disease?
Yes- if the antigen involved is a self-antigen.
What do Type III hypersensitivity reactions involve?
Formation of immune complexes.
What happens in Type III hypersensitivity reactions?
Soluble antigens bind with IgG in a ration that results in the accumulation of immune complexes (aggregates of antibody/antigen). These form on vascular epithelial cells and are not phagocytose so lead to a cascade of inflammatory events. (Mast cells, Complement, Permeability).
What are immune complexes?
Aggregates of antibody/antigen.
Where do immune complexes form?
Vascular epithelium of blood vessels.
Can immune complexes be phagocytosed?
What happens during the cascade of inflammatory events caused by immune complexes?
IgG stimulates mast cells
Complement activation- pro inflammatory C3a/C5a
Increased vascular permeability due to chemotactic recruitment of neutrophils and macrophages.
What is recruited in the complement activation in this inflammatory cascade?
C3a / C5a
Why is there an increased vascular permeability within the inflammatory cascade?
Chemotactic recruitment of neutrophils and macrophages.
How are immune complexes removed?
Lysosomal degradation- results in damage to local cells resulting in coagulation pathway activation.
Why is the coagulation pathway activated during Type III reactions?
Localised cell damage due to the lysosomal degradation of immune complexes.
What do Type IV hypersensitivity reactions involve?
Are Type IV reactions antigen-mediated?
No- regulated by T-cells and involve effector cells.
What happens during Type IV hypersensitivity reactions?
Involve tissue damage mediated by activated macrophages and cytotoxic T-cells.
What are the 3 types of Type IV reaction?
CD4 Th1- delayed
CD4 Th2- inhalation
CD8 cytotoxic T lymphocyte- transplant rejection
What happens during CD4 Th1 reactions?
What happens during TD4 Th2 reactions?
Soluble antigen is inhaled- eosinophil recruitment and activation occurs with cytokine and inflammatory mediator release. Cause of asthma / rhinitis.
What happens during CD8 cytotoxic T-lymphocyte reactions?
Cell killing and tissue injury- seen within tissue transplant rejection.
What is immunological tolerance?
Immunological tolerance is a state of tolerance in the immune system when it would usually be expected to excite an immunological response.
What is the difference between systemic autoimmune disease and tissue-specific autoimmune disease?
Systemic autoimmune disease involves the holistic system whereas tissue-specific autoimmune disease is localised.